Department of Neurology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China (mainland).
Department of Neurosurgery, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China (mainland).
Med Sci Monit. 2020 Mar 2;26:e921026. doi: 10.12659/MSM.921026.
BACKGROUND Alzheimer disease (AD) is a significant health issue for the elderly, and there are at present no clinically effective anti-AD agents. Prevention of Aß-induced neurotoxicity is proposed as a possible modality for treatment of AD. miR-33 has been proven to promote Aß secretion and impair Aß clearance in neural cells. The present study assessed whether miR-33 is involved in AD pathology. MATERIAL AND METHODS miR-33 level was detected by qRT-PCR. The Akt/mTOR pathway was analyzed by Western blot analysis. Neuron inflammation and oxidative stress were measured using commercial detection kits. Flow cytometry and Western blot assay were conducted to assess cell apoptosis, and Western blot assay was used to assess synaptic protein levels. RESULTS miR-33 expression level was markedly upregulated in SH-SY5Y cells treated with Aß₂₅₋₃₅. miR-33 knockdown suppressed inflammation, oxidative stress, and cell apoptosis. In addition, miR-33 knockdown improved synaptic plasticity, and the protective effect of miR-33 knockdown was discovered through suppressing activation of the Akt/mTOR signaling pathway. CONCLUSIONS Taken together, these findings suggest that miR-33 knockdown protects against Aß₂₅₋₃₅-induced inflammation, oxidative stress, apoptosis, and synaptic damage by suppressing activation of the Akt/mTOR pathway.
阿尔茨海默病（AD）是老年人面临的重大健康问题，目前尚无临床有效的抗 AD 药物。预防 Aβ诱导的神经毒性被认为是治疗 AD 的一种可能方法。miR-33 已被证明可促进神经细胞中 Aβ的分泌并损害 Aβ的清除。本研究评估了 miR-33 是否参与 AD 病理学。
通过 qRT-PCR 检测 miR-33 水平。通过 Western blot 分析评估 Akt/mTOR 通路。使用商业检测试剂盒测量神经元炎症和氧化应激。通过流式细胞术和 Western blot 检测评估细胞凋亡，Western blot 检测评估突触蛋白水平。
Aβ₂₅₋₃₅处理的 SH-SY5Y 细胞中 miR-33 的表达水平明显上调。miR-33 敲低可抑制炎症、氧化应激和细胞凋亡。此外，miR-33 敲低可改善突触可塑性，通过抑制 Akt/mTOR 信号通路的激活，发现 miR-33 敲低的保护作用。
综上所述，这些发现表明，miR-33 敲低通过抑制 Akt/mTOR 通路的激活，可防止 Aβ₂₅₋₃₅诱导的炎症、氧化应激、凋亡和突触损伤。
